Unconditioned response to an aversive stimulus as predictor of response to conditioned fear and safety: A cross-species study

Safety signals predict the non-occurrence of an aversive event, thereby inhibiting fear responses. Previous research has shown that conditioned safety learning is impaired in patients suffering from post-traumatic stress disorder (PTSD). Using a translational approach, the present study aimed to investigate whether individual responses to an aversive unconditioned stimulus (US) in rats (basic science), non-traumatized (pre-clinical) or traumatized humans (clinical) predicts their response to a conditioned fear or safety stimulus. Using three different archival datasets, the unconditioned response (UCR) to the US during fear or safety conditioning was assessed in rats, non-traumatized humans, and trauma-exposed humans. The response to learned fear (CS+; context) and safety (CS-) was measured by the modulation of the startle response (rats, traumatized humans) or skin conductance response (non-traumatized humans). Our results showed that all groups with low UCR and those with high UCR from the rodent or non-traumatized human samples displayed lower fear response to the CSthan to the CS+ . Traumatized humans with high UCR showed similarly high responses to the CS+ and CS-. While all groups showed a positive association between the UCR and CS+ response, the UCR correlated positively with the CSresponse in traumatized humans only. Our findings suggest that an elevated response to aversive stimuli predicts deficits in conditioned safety memory in those at risk for trauma-related disorders and confirms that impaired safety learning could be a valid biomarker for these diseases.

Automated summary

The study found that individuals with lower responses to aversive stimuli also displayed lower fear responses to conditioned safety stimuli, while traumatized individuals showed responses to fear and safety stimuli influenced by their unconditioned response to aversive stimuli.